DEPSCoR: Indentification of Genes that Influence Sleep & Wake Using a Novel High- Throughput, Piezoelectric Technology

Sleep, or some function of sleep, is essential for life, and even relativcly short periods of sleep deprivation lead to decreased reaction times and slowed cognition and mentation. Moreover, sleep loss is cumulative and the ability to sleep is compromised by circadian rhythms, stress. and irregular schedules - conditions that inevitably result from mobilizing troops, transporting them across time zones. and inserting them into action. Despite increasing knowledge about the regulation of sleep, the basic functions of sleep are still unknO\\Il. Given these unknO\\I1s, a genetic approach offers great potential. since clear genetic differences exist for many sleep parameters. and in theory these genes can be identitled with no other knowledge. For example. se\eral different inbred strains of mice sho\\' dramatic differences in total sleep time, response to sleep deprivation. and other variables. In addition to such natural or spontaneous genetic variations. mutagenesis can be used to alter genes, and the effects on sleep and wake assessed. However. a major limitation to genetic studies of sleep has been the time-consuming nature and other difficulties in performing EEG/EMG analyses. In mice, EEG/EMG studies require extensive surgery, recovery. adaptation to cabling. and considerable analysis of the resulting EEG patterns. To address many questions, a simple, high-throughput measure of sleep and wake would suffice, and enable studies that \\ere previously too tedious or difficult to perform. As described in this proposal. we have developed a technology using piezoelectric sensors that fulfills these basic needs, and that we believe will greatly facilitate the identification of critical sleep/wake related genes. We \\ill utilize genetic crosses between different inbred strains and take advantage of a large mutagcnesis program already underway at Oak Ridge "'ational Laboratorv. The identitlcation of genes that intluence sleep and wake could provide new targets for better wake promoting and sleep promoting drugs. or perhaps drugs that improve waking performance or sleep intensity. A better understanding of basic sleep functions and sleep regulation might also suggest non-phannacological approaches to such improvements. Improved treatment of sleep and circadian disorders (or disruptions caused by traveling across many time zones) might also be achieved. Clearly. maintaining high levels of performance in the face of sleep loss and circadian disruptions is especially critical for the military.